title: Molecular changes in the phosphatidylinositide 3-kinase (PI3K) pathway are common in gastric cancer.
abstract: OBJECTIVE
  The phosphatidylinositide 3-kinase (PI3K) pathway is an important signalling pathway that is frequently activated in cancer cells. This has led to the emergence of PI3K inhibitors as potential new treatment modalities for many cancers. We have investigated the frequency of molecular changes in the PI3K pathway in gastric cancer.
  
  
  METHODS
  A series of sixty one human gastric cancer specimens and nine human gastric cancer cell lines were screened for PIK3CA mutations and copy number gain by direct sequencing and multiplex ligation-dependent probe amplification (MLPA), respectively. PTEN protein levels were assessed by immunohistochemistry.
  
  
  RESULTS
  Alterations in the PI3K pathway were found in 33 of 61 (54%) gastric tumours. PIK3CA mutation and copy number gain were detected in 3 (4.9%) and 8 (13.1%), respectively, of 61 gastric cancer samples while PTEN loss was detected in 24 (39%) of the tumours. Two tumours had both PTEN loss and PIK3CA copy number gain. There were no significant associations between these PI3K pathway changes and the clinical features of the tumours.
  
  
  CONCLUSIONS
  Alterations in the PI3K pathway are frequent in gastric tumours implicating this pathway as a legitimate therapeutic target in gastric cancer.
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Thang N
authors.initials: TN
authors.lastname: Tran
authors.forename: Kate
authors.initials: K
authors.lastname: Brettingham-Moore
authors.forename: Cuong P
authors.initials: CP
authors.lastname: Duong
authors.forename: Catherine
authors.initials: C
authors.lastname: Mitchell
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Clemons
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Phillips
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PIK3CA; PTEN; gene amplification; mutation; tissue microarray